Kataegis, a recently discovered phenomenon in which multiple mutations cluster in a few hotspots in a genome, are a positive marker in breast cancer. Patients with kataegis have less invasive tumors and better prognoses.1

Kataegis are defined as 6 or more consecutive mutations that have average intermutation distances of 1 kilobase or less. They were first studied in breast cancer, where one or more kataegis locations occur in more than half of tumors.

"We don't know what causes kataegis, and before this study not much was known about its functional importance at the molecular or clinical level," said Kelly Frazer, PhD, professor of pediatrics and director of the Institute for Genomic Medicine at University of California San Diego School of Medicine and Moores Cancer Center, and senior author of the study. "We've now found that kataegis is associated with a good prognosis for patients with breast cancer."

Frazer and her research team analyzed whole-genome sequences of 97 breast tumors and their associated normal DNA that they obtained from The Cancer Genome Atlas (TCGA). The kataegis status of these 97 tumors was paired with patient data that included age at diagnosis, treatment, and outcome. They also examined an additional 412 human breast cancers for which they predicted kataegis status.

Several clinical factors were found to associate with kataegis. Kataegis were found to be more common in patients with breast cancer diagnosed at a later age, in patients with HER2-positive tumors, and in patients with high-grade tumors.

Kataegis are a marker for good prognosis, particularly when on chromosomes 17 and 22, which are associated with low tumor invasiveness. Patients with kataegis tended to die older (median age 78 years) than patients without kataegis (median age 47 years), although TCGA does not report causes of death.

"We think kataegis mutations are dampening the abnormal expression of neighboring genes that might otherwise contribute to tumor development and invasiveness," said Matteo D'Antonio, PhD, a postdoctoral researcher in Frazer's lab and first author of the study.

The hope is that, eventually, kataegis status could help doctors determine the treatment options that might work best for patients with the mutation pattern.